WO2012043393A1

WO2012043393A1 - Emulsion composition

Info

Publication number: WO2012043393A1
Application number: PCT/JP2011/071658
Authority: WO
Inventors: 和克阿度
Original assignee: 小林製薬株式会社
Priority date: 2010-09-30
Filing date: 2011-09-22
Publication date: 2012-04-05
Also published as: JP5912238B2; JP2012077027A

Abstract

[Problem] To provide an emulsion composition, an external skin preparation, and an analgesic, each of which is in a semi-solid state, has excellent thermal stability, and gives a good use sensation when applied to the skin. [Solution] An emulsion composition containing water, an oily component, a hydrophilic surfactant, and terpene, characterized in that the oily component is contained in an amount of 0.2 to 0.7 parts by weight with respect to 1 part by weight of the water, and the hydrophilic surfactant and the terpene are contained in amounts of 0.37 to 1.0 parts by weight and 0.08 to 0.45 parts by weight with respect to 1 part by weight of the oily component, respectively.

Description

Emulsified composition

The present invention relates to an emulsified composition, an external preparation for skin, and an analgesic.

Conventionally, emulsification techniques have been widely used to stably mix water and oil (fats) that normally do not mix with each other, and emulsifiers that reduce the interfacial tension between water and oil are used to obtain stable emulsion compositions. Has been. For example, an oil-in-water emulsion composition in which oil components are dispersed in water is a mixture of water and oil components stably by the action of the emulsifier, and is widely used in pharmaceuticals, cosmetics, etc. as high-value-added preparations. ing. *

However, such an emulsified composition contains both water and oil, which are inherently difficult to stably mix, and is generally known to be thermodynamically unstable. It is a big issue. In particular, when the emulsified preparation exhibits a feeling of use and a therapeutic effect depending on the application, there is always a problem of ensuring the stability of the composition, so the type of emulsifier, the heating conditions during the production of the emulsified composition, Various studies such as cooling conditions have been made. *

Also, for stiff shoulders and muscle fatigue, when using ointments, creams, gels, etc. containing active ingredients, there are problems such as being hard and difficult to apply, and having skin irritation, etc. It is desired to provide an emulsified composition that has high thermal stability and does not cause such problems. *

Patent Document 1 discloses a skin external preparation composition containing an ester steroid and menthol, which are effective as a therapeutic agent for atopic dermatitis. However, only creams are shown here that do not require stability.

JP 2009-184951 A

Another object of the present invention is to provide an emulsified composition, an external preparation for skin, and an analgesic that solve the above-mentioned problems and are excellent in heat stability in a semi-solid state and have a good feeling when applied to the skin. .

The present invention is an emulsified composition containing water, an oily component, a hydrophilic surfactant and a terpene, wherein the oily component is added in an amount of 0.2 to 0.7 parts by weight with respect to 1 part by weight of the water. The present invention relates to an emulsion composition comprising 0.37 to 1.0 part by weight of the hydrophilic surfactant and 0.08 to 0.45 part by weight of the terpene with respect to 1 part by weight of an oil component. *

In the emulsified composition, the oil component is preferably liquid at normal temperature. The oily component preferably contains liquid paraffin in an amount of 25% by weight or more in 100% by weight of the oily component. Further, the hydrophilic surfactant preferably contains 30% by weight or more of polyoxyethylene cetyl ether of HLB 8 to 13.5 in 100% by weight of the hydrophilic surfactant. *

In the emulsion composition, the terpene is preferably a monoterpene. Here, the monoterpene is preferably a cyclic monoterpene. Moreover, it is preferable that the said emulsion composition is an oil-in-water type emulsion composition. *

This invention is also a skin external preparation which consists of the said emulsion composition. The present invention is also an analgesic comprising the above emulsion composition.

Since the present invention is an emulsified composition containing specific amounts of water, an oil component, a hydrophilic surfactant and a terpene, it is excellent in thermal stability in a liquid to semi-solid state and is applied to the skin. The feeling when used is also good.

The emulsified composition of the present invention contains water, an oily component, a hydrophilic surfactant and a terpene in specific amounts. *

When a compound that can be used as a refreshing agent or a fragrance component is applied to an emulsion stabilizer for essentially different uses, it usually tends to reduce stability. In the present invention, among these compounds, a specific compound called terpene is used, and since the terpene is mixed with water, an oil component, and a hydrophilic surfactant in specific amounts, the heat stability is extremely high. An emulsified composition (emulsified preparation) excellent in the above can be prepared. *

Thus, the use of an emulsion stabilizer has not been known so far, but terpenes, which have been known to be destabilized, are limited to emulsion compositions of a specific formulation as in the present invention as stabilizers. The knowledge of functioning is contrary to conventional technical common sense and has an effect that cannot be predicted at all. Furthermore, finding specific formulations using such terpenes is associated with great difficulty. *

Examples of water that can be used in the present invention include purified water, distilled water, sterilized water, physiological saline, deep sea water, and the like, preferably purified water. *

In the present invention, the oil component (oil phase) is a component constituting the oil droplets (oil phase) of the emulsion composition (oil-in-water emulsion composition). For example, olive oil, wheat germ oil, rice bran oil, safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, peanut oil are commonly used in pharmaceuticals, quasi drugs, cosmetics, etc. Vegetable oil such as lard, fish oil, animal oil such as squalane and beeswax, liquid paraffin, gelled hydrocarbon, mineral oil such as petrolatum, lecithin derivatives such as soybean lecithin, isopropyl myristate, isopropyl palmitate, cetyl palmitate, sebacic acid Fatty acid esters such as diethyl and ethyl oleate, silicones such as dimethyl silicone and cyclic silicone, fatty acids such as oleic acid and linoleic acid, hormones such as ethinyl estradiol, fennel oil, clove oil, peppermint oil, eucalyptus oil, Essential oils such as lemon oil And the like. Silicon oil, waxes and the like are also included. *

Moreover, higher alcohol is mentioned as another oil-based component. Examples of the higher alcohol include aliphatic alcohols having 6 or more carbon atoms. Specific examples include cetanol, behenyl alcohol, myristyl alcohol, cetyl alcohol, oleyl alcohol, stearyl alcohol, hexadecyl alcohol, lanolin alcohol and the like. *

The oil component is preferably liquid at room temperature (25 ° C.) from the viewpoint of ensuring the fluidity of the emulsion composition. Among the oil components, vegetable oils, animal oils, mineral oils, and fatty acid esters are preferable, and animal oils, mineral oils, and fatty acid esters are more preferable because an emulsion composition having excellent heat stability and fluidity can be prepared. preferable. In particular, liquid paraffin is preferably used alone or in combination as a mineral oil. Furthermore, it is preferable to mix | blend the said higher alcohol with these components. An oil component may be used independently and may use 2 or more types together. *

In the emulsion composition of the present invention, the blending amount of the oil component is 0.2 to 0.7 parts by weight, preferably 0.22 to 0.50, based on 1 part by weight of water from the viewpoint of thermal stability. Part by weight, more preferably 0.22 to 0.45 part by weight. *

Moreover, in the emulsion composition of this invention, it is preferable to contain 25 weight% or more of liquid paraffin in 100 weight% of oily components. Thereby, the outstanding thermal stability and fluidity | liquidity are obtained. More preferably, it is 27 weight% or more, More preferably, it is 29 weight% or more. On the other hand, the upper limit is not particularly limited, but is preferably 90% by weight or less, more preferably 80% by weight or less. *

The hydrophilic surfactant preferably has an HLB of 8 to 18.0, more preferably 8 to 13.5. HLB is an abbreviation for hydrophile-lipophile balance, and is known as one of the indexes representing the effect of surfactants. The higher the HLB value, the higher the hydrophilicity. In the present invention, HLB refers to a value calculated by the Davies formula, HLB = 7 + Σ (the number of hydrophilic groups) −Σ (the number of lipophilic groups). Moreover, when containing 2 or more types of surfactant, a weighted average value is said. *

The hydrophilic surfactant is not particularly limited as long as it is usually used in pharmaceuticals, quasi drugs, cosmetics, etc. From the viewpoint of thermal stability and fluidity, a nonionic hydrophilic surfactant is used. preferable. As the nonionic hydrophilic surfactant, a polyoxyethylene (hereinafter referred to as POE) addition type surfactant is suitable, for example, POE (10 to 50 mol) phytosterol ether, POE (10 to 50 mol) dihydro Cholesterol ether, POE (10-50 mol) 2-octyldodecyl ether, POE (10-50 mol) decyl tetradecyl ether, POE (10-50 mol) oleyl ether, POE (10-50 mol) cetyl ether, POE ( Polyoxyethylene alkyl ethers such as 5-30 mol) polyoxypropylene (5-30 mol) 2-decyltetradecyl ether, POE (10-50 mol) polyoxypropylene (2-30 mol) cetyl ether; Acid / phosphate (POE cetyl ether phosphorus POE (20-60 mol) sorbitan monooleate, POE (10-60 mol) sorbitan monoisostearate, POE (10-80 mol) glyceryl monoisostearate, POE (10-30 mol) glyceryl mono Stearate, POE (20-100) castor oil, POE (20-100) POE / polyoxypropylene modified silicone, POE / alkyl modified silicone, polyethylene glycol monolaurate, polyethylene glycol monopalmitate, polyethylene glycol monostearate, dilaurin Polyethylene glycol acid, polyethylene glycol dipalmitate, polyethylene glycol distearate, polyethylene glycol dioleate, polyethylene glycol diricinoleate Etc., and the like. *

Among them, from the viewpoint of thermal stability, polyoxyethylene cetyl ether, a mixture of this and polyethylene glycol mono (di) stearate, polyoxyethylene cetyl ether sodium phosphate, one or more polyoxyethylene polyoxypropylene cetyl ethers These compounds are preferably blended, those having an HLB of 8 to 13.5 are more preferred, and polyoxyethylene cetyl ether having an HLB of 8 to 13.5 is particularly preferred. A hydrophilic surfactant may be used independently and may use 2 or more types together. *

In the emulsified composition of the present invention, the blending amount of the hydrophilic surfactant is 0.37 to 1.0 part by weight, preferably 0.39 with respect to 1 part by weight of the oil component, from the viewpoint of thermal stability. Is 0.91 part by weight, more preferably 0.42 to 0.75 part by weight. *

In the emulsified composition of the present invention, it is preferable to contain 30% by weight or more of polyoxyethylene cetyl ether of HLB 8 to 13.5 in 100% by weight of the hydrophilic surfactant. Thereby, the outstanding thermal stability and fluidity | liquidity are obtained. More preferably, it is 33% by weight or more. On the other hand, the upper limit is not particularly limited, but is preferably 90% by weight or less, more preferably 80% by weight or less. *

Terpenes (acyclic compounds, cyclic compounds (monocyclic, bicyclic, etc.) include monoterpenes, hemiterpenes, sesquiterpenes, etc., specifically, terpene hydrocarbons, terpene series Examples include alcohols, terpene aldehydes, and terpene ketones.

Examples of the terpene hydrocarbon include monoterpene hydrocarbons such as limonene, pinene and camphor, and sesquiterpene hydrocarbons such as lysine. Examples of the terpene alcohol include monoterpene alcohols such as citronellol, geraniol, linalool, menthol, terpineol, and borneol, sesquiterpene alcohols such as farnesol, diterpene alcohols, and the like. Examples of the terpene aldehyde include monoterpene aldehydes such as citronellal, citral and safranal, and diterpene aldehydes such as retinal. Examples of terpene ketones include monoterpene ketones such as menthone, carbomenton, and yonon. These terpenes may be any of d-, l- and dl-forms. *

Among these, from the viewpoint of thermal stability, monoterpenes are preferable, and cyclic monoterpenes are more preferable. A terpene may be used independently and may use 2 or more types together. *

In the emulsified composition of the present invention, the blending amount of the terpene is 0.08 to 0.45 parts by weight, preferably 0.08 to 0.43 parts per 1 part by weight of the oil component from the viewpoint of thermal stability. Parts by weight, more preferably 0.08 to 0.39 parts by weight.

The viscosity of the emulsified composition of the present invention is preferably 4000 to 150,000 cP, more preferably 10,000 to 130,000 cP, from the viewpoints of thermal stability and usability upon application to the skin. The viscosity is a value measured by the following method using a viscometer “model: LVDV-II + (BROOK FIELD, manufactured by Spindle E type)”. (Method) 35 g of a sample (emulsified composition) is placed in a sample container of a Maruemu screw tube (No. 7) and measured at 4.0 RPM while moving up and down at room temperature (around 25 ° C.). The intermediate value is used as the measured value. *

Although it does not specifically limit as a method to manufacture the emulsion composition of this invention, For example, it can manufacture as follows. Water, oil component, hydrophilic surfactant, terpene, and other ingredients such as medicinal ingredients, higher alcohols, and fragrances are mixed as necessary, heated to 65.0-85.0 ° C, and then mixed with a homogenizer The emulsified product of the present invention can be prepared by emulsification by a known method such as emulsification under a predetermined condition using a machine. *

If it is a range which does not impair the effect of this invention, if it is a range which does not impair the effect of this invention, according to the form etc., it can select suitably another component and can mix | blend 1 type or 2 or more types together. For example, various additives such as stabilizers, thickeners, preservatives, buffers, pH adjusters and the like that are commonly used in the preparation of liquids and semi-solids can be mentioned. Can be mentioned. *

Stabilizer: Dibutylhydroxytoluene, sodium edetate, sodium sulfite, dry sodium sulfite and the like. *

Thickener: xanthan gum, hypromellose (hydroxypropylmethylcellulose), hydroxypropylcellulose, macrogol 400, macrogol 1500, macrogol 4000, carboxyvinyl polymer and the like. *

Preservatives: butyl paraben, methyl paraben, propyl paraben, ethyl paraben, sodium benzoate, benzyl alcohol and the like. *

Buffer: borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, aspartic acid, aspartate, etc. *

pH adjusters: inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid; lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, Organic acids such as aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid; inorganic bases such as sodium hydrogen carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, calcium hydroxide, magnesium hydroxide; monoethanolamine, Organic salts such as triethanolamine, diisopropanolamine, triisopropanolamine and lysine. *

Others: Sodium carboxymethyl starch, magnesium stearate, cellulose, lactose, hard fat, self-emulsifying glyceryl monostearate, glyceryl stearate, D-sorbitol, medium chain fatty acid triglyceride, corn starch, propylene glycol, propylene glycol fatty acid ester, 1,3-butylene glycol, glycerin, polyethylene glycol, glyceryl monostearate and the like. *

The form of the emulsified composition of the present invention is a liquid to semi-solid oil-in-water emulsified composition, which contains medicinal ingredients and the like according to the affected area, application method, etc. to be applied, and is appropriately set. It can be suitably used as an external preparation for skin, and a therapeutic effect can be obtained. In addition, the emulsified composition has fluidity in a liquid to semi-solid state, so that it is easy to take in use, has good spreadability, has little stickiness, is easy to adjust to the skin, and has little irritation. Therefore, it can be suitably applied to a layer such as women who place importance on sensory elements such as tactile sensation and vision. *

Specific examples of the external preparation for skin include liquid to semisolid creams, emulsions, lotions and the like. Among these, preferable forms include emulsions and lotions. In particular, it can be suitably used as an analgesic. Specifically, as an anti-inflammatory analgesic, it is possible to loosen or heal muscles by applying to the affected area of stiff shoulders or muscle fatigue. *

The above-mentioned external preparation for skin can be blended with active ingredients as long as the effects of the present invention are not impaired. Examples of active ingredients include steroids (dexamethasone, dexamethasone hydrochloride, dexamethasone acetate, hydrocortisone hydrochloride, prednisolone valerate, prednisolone acetate, etc.), antihistamines (diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), local anesthetics (lidocaine) , Dibucaine, procaine, tetracaine, bupipacaine, mepipacaine, chloroprocaine, proparacaine, meprilucaine or a salt thereof, alkyl benzoate (for example, ethyl aminobenzoate, diethylaminoethyl parabutylaminobenzoate hydrochloride), orthocaine, oxesasein, oxypolyene Toxicdecane, funnel extract, percamin ase, tesit decite, etc.), anti-inflammatory agents (glycyrrhetinic acid, glycyl) Dipotassium stannate, monoammonium glycyrrhetinate, allantoin, salicylic acid, glycol salicylate, methyl salicylate, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), bactericides (benzalkonium chloride, decalinium chloride, benzethonium chloride, cetylpyridinium chloride, Isopropylmethylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate, aqueous ammonia, sulfadiazine, lactic acid, phenol, etc.), antipruritic agents (crotamiton, thianthol, etc.), skin protectants (collodion, castor oil, etc.), blood circulation promoting ingredients (nonyl acid vanillylamide, Nicotinic acid benzyl ester, capsaicin, red pepper extract, vitamin E), vitamins (vitamin A, B, C, D, etc.), Co polysaccharides (sodium chondroitin sulfate, glucosamine, hyaluronic acid and the like) and the like. *

When the above-mentioned external preparation for skin is used as an analgesic for reducing or relieving physical pain, such physical pain is not particularly limited, but is caused by external stimuli such as trauma, aging, or poor It may be caused by things such as posture, long working hours, maintaining a stationary posture for a long time, excessive exercise, or mental stress. Examples of the pain that can be treated include neuralgia, joint pain, low back pain, muscle pain, stiff shoulder pain, fracture pain, bruise pain, sprain pain, trauma pain, headache, post-operative pain and the like. Preferred are neuralgia, low back pain, muscle pain, stiff shoulder pain, and joint pain caused by aging, poor posture, long working hours, etc., and more preferred are low back pain, muscle pain, stiff shoulder pain, and joint pain. Moreover, in addition to analgesia, it can be used for the purpose of anti-inflammation (anti-inflammatory) and / or fatigue and fatigue.

The present invention will be specifically described based on examples, but the present invention is not limited to these examples. *

(Examples 1 to 14 and Comparative Examples 1 to 8) According to the prescriptions shown in Tables 1 to 3, the ingredients were mixed and heated to 65 ° C. or higher, and then homogenizer “ROBOMICS (manufactured by TOKUSYU KIKA)” Emulsification was performed at 12,500 rpm for 3 minutes. Then, it cooled to room temperature, stirring, and obtained the emulsion composition. *

In addition, HLB of each hydrophilic surfactant and a brand name are as follows. Polyoxyethylene cetyl ether (BC-5.5): HLB = 10.5 (manufactured by Nikko Chemicals) Polyoxyethylene cetyl ether (BC-2): HLB = 8 (manufactured by Nikko Chemicals) polyoxyethylene cetyl ether ( BC-10): HLB = 13.5 (manufactured by Nikko Chemicals) Polyoxyethylene cetyl ether (BC-23): HLB = 18 (manufactured by Nikko Chemicals) Polyethylene glycol monostearate-100: HLB = 18 (Nikko Chemicals) (Made by company)

The thermal stability of the obtained emulsion composition was evaluated by the following method. Moreover, the viscosity of the emulsion composition was measured by the above-mentioned method. The results are shown in Tables 1-3. *

(Thermal stability) After leaving the obtained emulsified composition for one day, it is heated in a 70 ° C hot water bath, and the time until property change (occurrence of fault / separation) is measured. evaluated. In addition, the thing which isolate | separated and generate | occur | produced after leaving still for 1 day was set to 0 second. ◎: 1200 seconds or more ○: 600 seconds or more and less than 1200 seconds ×: less than 600 seconds

From the results of Example 5 and Comparative Example 1, it was revealed that l-menthol exhibited an action of stabilizing the emulsion composition. In addition, in Examples 1 to 3 and 11 and Comparative Examples 2 to 3, it was proved that the stabilizing effect was exhibited by adjusting l-menthol to a specific amount. Further, from Comparative Examples 4 to 6, it has become clear that it is important to adjust the hydrophilic surfactant to a specific amount and from Comparative Examples 7 to 8 to adjust the oil component to a specific amount. *

A good stabilizing action was exhibited by using POE cetyl ether having an HLB of 8 to 13.5 (Examples 5 to 10). Examples 12 to 14 also showed that dl-camphor, geraniol, and limonene also exhibited the same stabilizing action as l-menthol. *

(Examples: Examples 15 to 19 and Comparative Examples 9 to 10) In accordance with the formulation shown in Table 4, the ingredients were mixed and heated to 65 ° C. or higher, and then homogenizer “ROBOMICS (manufactured by TOKYUSU KIKA)” Emulsification was performed at 12,500 rpm for 3 minutes. Then, it cooled to room temperature, stirring, and prepared the emulsion composition (anti-inflammatory analgesic). The obtained preparation was evaluated in the same manner as described above, and the results are shown in Table 4. *

The same effect was also demonstrated for the preparation by adjusting l-menthol to a specific amount. In addition, it is clear that the liquid paraffin content in the oily component and the POE cetyl ether content in which the HLB in the hydrophilic surfactant is 8 to 13.5 are more than a specific value, so that a sufficient stabilizing effect is obtained. became.

Claims

An emulsified composition comprising water, an oil component, a hydrophilic surfactant and a terpene, wherein 0.2 to 0.7 parts by weight of the oil component and 1 part by weight of the oil component with respect to 1 part by weight of the water An emulsified composition comprising 0.37 to 1.0 part by weight of the hydrophilic surfactant and 0.08 to 0.45 part by weight of the terpene with respect to parts.
The emulsified composition according to claim 1, wherein the oil component is liquid at normal temperature.
The emulsion composition according to claim 1 or 2, wherein the oily component contains 25% by weight or more of liquid paraffin in 100% by weight of the oily component.
The emulsion composition according to any one of claims 1 to 3, wherein the hydrophilic surfactant contains 30% by weight or more of polyoxyethylene cetyl ether of HLB 8 to 13.5 in 100% by weight of the hydrophilic surfactant.
The emulsified composition according to any one of claims 1 to 4, wherein the terpene is a monoterpene.
The emulsion composition according to claim 5, wherein the monoterpene is a cyclic monoterpene.
The emulsion composition according to any one of claims 1 to 6, wherein the emulsion composition is an oil-in-water emulsion composition.
An external preparation for skin comprising the emulsion composition according to any one of claims 1 to 7.
An analgesic comprising the emulsion composition according to any one of claims 1 to 7.